Theheartispartiallyorcompletelydenervatedinvariousclinicalsituations:(1)asurgicallytransplantedheartistotallydenervated,althoughtheintrinsic,postganglionicparasympatheticfiberspersist;(2)atropineblocksvagaleffectsontheheart,andpropranololblockssympatheticβ-adrenergicinfluences;(3)certaindrugs,suchasreserpine,depletecardiacnorepinephrinestoresandtherebyrestrictorabolishsympatheticcontrol;and(4)inchroniccongestiveheartfailure,cardiacnorepinephrinestoresareoftenseverelydiminished,andanysympatheticinfluencesareattenuated.
Two principal intrinsic mechanisms, the Frank-Starling mechanism and rate-induced regulation, enable the myocardium to adapt to changes in hemodynamic conditions. The Frank-Starling mechanism (Frank-Starling law of the heart) is invoked in response to changes in the resting length of myocardial fibers. Rate-induced regulation is evoked by changes in the frequency of the heartbeat.
CHAPTER 18 Regulation of the Heart and Vasculature
In the 1910s, the German physiologist Otto Frank and the English physiologist Ernest Starling independently studied the response of isolated hearts to changes in preload and afterload (see
Chapter 16).
When ventricular filling pressure (preload) is increased, ventricular volume increases progressively, and after several beats, becomes constant and larger. At equilibrium, the volume of blood ejected by the ventricles (stroke volume) with each heartbeat increases to equal the greater quantity of venous return to the right atrium.
The increased ventricular volume facilitates ventricular contraction and enables the ventricles to pump a greater stroke volume. This increase in ventricular volume is associated with an increase in length of the individual ventricular cardiac fibers. The increase in fiber length alters cardiac performance mainly by altering the number of myofilament cross-bridges that interact (see
Chapter 16).
More recent evidence indicates that the principal mechanism involves a stretch-induced change in the sensitivity of cardiac myofilaments to Ca++ (see ). There exists an optimal fiber length, however. Excessively high filling pressures that overstretch the myocardial fibers may depress rather than enhance the pumping capacity of the ventricles (see
Fig. 16.36
Starling also showed that isolated heart preparations could adapt to changes in the counterforce to the ventricular ejection of blood during systole (i.e., afterload). As the left ventricle contracts, it does not eject blood into the aorta until the ventricle has developed a pressure that just exceeds the prevailing aortic pressure (see
Fig. 16.39 ). The aortic pressure during ventricular ejection essentially constitutes the left ventricular afterload. In Starling’s experiments, arterial pressure was controlled by a hydraulic device in the tubing that led from the ascending aorta to the right atrial blood reservoir. To hold venous return to the right atrium constant, the hydrostatic level of the blood reservoir was maintained. As Starling raised arterial pressure to a new constant level, the left ventricle responded at first to the increased afterload by pumping a diminished stroke volume. Because venous return was held constant, the diminution in stroke volume was accompanied by a rise in ventricular diastolic volume, as well as by an increase in the length of the myocardial fibers. This change in end-diastolic fiber length finally enabled the ventricle to pump a normal stroke volume against the greater peripheral resistance. As mentioned, a change in the number of cross-bridges between the thick and thin filaments probably contributes to this adaptation, but the major factor appears to be a stretch-induced change in the sensitivity of the contractile proteins to Ca++ .